1a: Exaggerated reactivity of the amygdala, a deep brain structure critical for coordinating our responses to danger, has been documented in almost all common forms of mental illness. More importantly, exaggerated amygdala reactivity predicts who may experience mental illness in response to future stress. Thus, amygdala reactivity could be useful as a risk biomarker in evolving efforts to help prevent mental illness. However, direct measurement of amygdala reactivity using functional MRI is neither easy nor inexpensive. We propose to establish a genetic signature of threat-related amygdala reactivity to overcome this measurement limitation using easy and inexpensive collection of DNA.

1b: Our proposed research promises to generate a readily assayed biomarker of risk for common mental illness, especially stress-related disorders such as depression and anxiety.

1c: We will combine genome-wide SNP and threat-related amygdala reactivity data from the UK BioBank with our own nearly identical data to conduct the first ever GWAS of this critical brain response.